Is RDX p.Pro86Ala (c.256C>G) pathogenic?

RDX p.Pro86Ala (c.256C>G) is classified Uncertain significance in RDX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). AlphaMissense: likely pathogenic (0.9092); Ultra-rare (popmax 0.0802%, sas).

How common is RDX p.Pro86Ala (c.256C>G) in the general population?

RDX p.Pro86Ala (c.256C>G) is ultra-rare (popmax 0.0802%, sas) (gnomAD).

What do computational predictors say about RDX p.Pro86Ala (c.256C>G)?

AlphaMissense predicts likely pathogenic (score 0.9092) — an in-silico prediction, not a clinical call.

RDX p.Pro86Ala

c.256C>G · rs376418131 · VCV229198

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9092	likely pathogenic
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -10.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0802% South Asian · 73/90,984 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00763% 123/1,611,112 alleles · ultra-rare exomes 114/1,458,936 · genomes 9/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0802%	1,246
Remaining individualsnot grpmax-eligible	0.0224%	4,455
Middle Eastern	0.0165%	6,076
Finnishnot grpmax-eligible	0.00312%	32,014
European (non-Finnish)	0.00263%	37,985
East Asian	0.00223%	44,866
African / African-American	0.00134%	74,792

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RDX
Protein: p.Pro86Ala
Coding: c.256C>G
MANE Select: NM_002906
dbSNP: rs376418131
Type: single nucleotide variant
Location: chr11:110264171 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 86: the ferm domain

Full RDX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RDX c.*156A>G Uncertain significance ★★ same type
RDX c.*2006A>G Uncertain significance ★★ same type
RDX c.*79A>C Uncertain significance ★★ same type
RDX p.Ala126Pro Uncertain significance ★★ ⚠ same type
RDX p.Ala442Thr Uncertain significance ★★ ⚠ same type
RDX p.Arg156Cys Uncertain significance ★★ ⚠ same type
RDX p.Arg342Cys Uncertain significance ★★ ⚠ same type
RDX p.Arg342His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rdx-p-pro86ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown